Abstract P139: Heart Failure Is Initiated By and Progresses Because of Normal Responses of Energy Metabolism to Stress
Objectives The mechanism underlying heart failure (HF) after an index cardiac event is unknown but should have several characteristics. HF is a modern problem, so it will likely be a general response and be able to encompass the variety of initiating cardiac lesions as well as significant stress (e.g. exertion). The consequences should lead to the many alterations found in HF.
[ATP] falls when energy demand outstrips supply (e.g. ischemia) but do not recover promptly with reperfusion because AMP is quickly catabolized and unavailable for recharging. [ATP] recovery is slow and limited by the availability of ribose-5-P. Ribose is not used as fuel and is channeled into nucleotide (ATP) synthesis allowing the effects of [ATP] recovery on function to be studied. Our hypothesis was that HF results from these responses of energy metabolism to stress which lower [ATP[ and affect the numerous myocardial reactions whose activity depends on [ATP]. The ability of ribose to quickly increase [ATP] allows these effects to be studied.
Methods The effects of ribose infusion on two models of myocardial stress were studied. (1) An intact canine model of global ischemia which allowed serial myocardial biopsies and detailed function analysis. (2) A rat myocardial infarction model which allowed ECHO analysis of the remote myocardium.
Conclusions 1) When energy demand outstripped supply (either from ischemia or increased work) myocardial [ATP] falls and recovery was slow. 2) Ribose is the limiting precursor for [ATP] recovery and infusion allowed the relationship between [ATP] and function to be studied. 3) In both myocardial ischemia recovery and increased load (from MI) ribose enhanced [ATP] and improved function. 4) The response of myocardial energy metabolism response to stress results in lower [ATP] which will decrease the activity of many function related reactions. 5) HF could begin and progress from these reactions of energy metabolism to cardiac stress.
- © 2011 by American Heart Association, Inc.